Retinal and choroidal TGF-β in the tree shrew model of myopia: Isoform expression, activation and effects on function

A visually evoked signalling cascade, which begins in the retina, transverses the choroid, and mediates scleral remodelling, is considered to control eye growth. The ubiquitous cytokine TGF-β has been associated with alterations in ocular growth, where alterations in scleral TGF-β isoforms mediate the scleral remodelling that results in myopia. However, while the TGF-β isoforms have been implicated in the scleral change during myopia development, it is unclear whether alterations in retinal and choroidal isoforms constitute part of the retinoscleral cascade. This study characterised the retinal and choroidal TGF-β isoform profiles and TGF-β2 activation during different stages of myopia development, as induced by form deprivation, in a mammalian model of eye growth. Using quantitative real-time PCR, the mRNA for all three mammalian isoforms of TGF-β was detected in tree shrew retina and choroid. Distinct tissue-specific isoform profiles were observed for the retina (TGF-β1:TGF-β2:TGF-β3 = 20:2085:1) and choroid (TGF-β1:TGF-β2:TGF-β3 = 16:23:1), which remained constant over the development period under investigation. The active and latent pools of retinal TGF-β2 were quantified using ELISA with the majority (>94%) of total TGF-β2 found in the latent form. Unlike previous scleral data showing early and continuous decreases in TGF-β isoform expression during myopia development, the levels of the three isoforms remained within normal ranges for retinal (TGF-β1, −14 to +14%; TGF-β2, −2 to +20%; TGF-β3, −10 to +26%) and choroidal (TGF-β1, −19 to +21%; TGF-β2, −26 to +8%; TGF-β3, −11 to +28%) tissues during myopia development (induction times of 3 h, 7 h, 11 h, 24 h, and 5 days). A 40% decrease in retinal TGF-β2 activation was observed after 5 days of myopia development, however, there was no functional correlate of altered TGF-β2 activity, as assessed by the retinal ERG response. Overall, these data highlight the specific nature of TGF-β isoform expression, which reflects the differences in tissue structure and function. While TGF-β isoforms are involved in scleral regulation during myopia development in mammals, they do not have a primary role in the retinal and choroidal signals. Thus, the regulation of eye growth via the retinoscleral cascade involves more than one factor, which is likely to be tissue-specific in nature.